IE44736B1 - Vaginal ring - Google Patents

Abstract

The present invention provides in a composite vaginal ring containing a safe and effective amount of a pharmaceutically active medicament which includes: a) a major supporting medicament-free vaginal ring consisting essentially of a physiolocigally acceptable synthetic resin and having at least a portion of the annular surface thereof adapted to mate with a corresponding minor, medicament-containing vaginal ring segment; and b) at least one minor, medicament-containing vaginal ring segment adapted to mate with the modified annular surface of said major supporting vaginal ring and consisting essentially of a safe and effective amount of a pharmaceutically active non-ionic, lipophilic drug dissolved or uniformly suspended in an elastomeric, cross-linked LTV linear dimethylpolysiloxane resin, the improvement wherein: at least one of the major supporting vaginal ring and the minor vaginal ring segment has a reniform or ellipsoidal cross section; or the major supporting vaginal ring is formed as a closed or inwardly open hollow-profile ring, as a closed or inwardly open hollow ring, as a hollow ring having a circular or reniform cross section, as a core-encased composite ring or as a sandwich element.

Description

This invention relates to vaginal ring devices and is an improvement in, or modification of, the invention forming the subject of Irish Patent Specification Wo. 42345, in which there is described and claimed a vaginal ring device which comprises a support-ring and at least one ring5 section extending circumferentially round a part or the whole of the support-ring and incorporating a pharmacologically active substance, the ring-section or sections being composed of an LTV - silicone elastomer material and being so located that the material has an exposed surface.

Vaginal rings that contain gestagenically active steroid hormones or a combination of gestagenically and oestrogenically active medicaments and which prevent conception with or without inhibiting ovulation, are used when pharmaceutical preparations for oral administration containing such active substances cannot be used for any of a wide variety of reasons, for example, where the person concerned has an aversion to taking a tablet. Vaginal rings also have the advantage that a woman is relieved of the necessity of having to take tablets daily. It is a ring-shaped structure simple to apply which is introduced into the vagina and is well tolerated by women. As compared with the known intra-uterine pessaries and capsules applied subcutaneously, they have the further advantage that at any time they can be removed and reinserted by the woman. Vaginal rings made from synthetic plastics, especially those based on silicone elastomers which are obtained from RTV-silicone rubber twocomponent compositions (Contraception 8 (1973) 651) or which are based on silicone rubber hot vulcanizates (Steroids 21^ (1973) 325), and which contain pharmacologically active substances such, for example, as steroid hormones, are known (Fertil. Steril. 21 (1970) 99. Amer. J. Obstet. - 2 4 Gynecol. 113 (1972) 927; Contraception 8 (6) (1973) 561; DT OS 1,900,196). The active substance is released from the synthetic plastics carrier over a long period and is absorbed by the vaginal mucosa.

The steroid hormones contained in the hitherto known vaginal rings have been exclusively those having a gestagenic action. Depending on the magnitude of the rate of release of the active substance by the vagina! rings, there is produced by their use protection against conception with or without the inhibition of ovulation.

However, contraceptives in the form of hitherto known vaginal rings have disadvantages. Inter alia, they are based on RTV (room temperature vulcanizing)-silicone rubber two-component compositions which, as is known, have poor mechanical properties. The mechanical properties of RTV-vulcanizates must first be improved by the addition of fillers.

These fillers, however, may impair the release of active substance from the vaginal ring. A few of the known vaginal rings are made by the vulcanization of suspensions of active substance in RTV-silicone rubber two-component compositions in the appropriate shapes. The active substances are released from this type of vaginal ring during the period of use in quantities that decrease considerably with time (Contraception 8 (1973) 561).

Considerable differences in the dosage of active substance inevitably result in qualitative and quantitative differences in the biological or contraceptive action and also in the nature and magnitude of undesired side effects during the period of use of the vaginal rings. Known vaginal rings, which contain the active ingredient homogeneously suspended in the synthetic plastics base, have a total weight of from around 6.0 to - 3 44 73<ϊ .0 grams. If the active substance is to be released from these vaginal rings during the period of use in a quantity sufficient for the desired action, they must contain in the region of from 5 to 30%' by weight of the active substance. In relation to the quantity of active substance released during the period of use, this is an uneconomically high content of the substance in the device.

Furthermore, no method is yet known for regulating the magnitude of the rate of release desired for a particular pharmacologically active substance from such vaginal rings based on silicone elastomer.

Some of the known vaginal rings are based on synthetic plastics that are physiologically not entirely unobjectionable. Thus, for the manufacture of some vaginal rings,there have been used RTV-silicone rubber two-component compositions containing tin compounds as vulcanization accelerators which have a toxic action on the living organism (Amer.J. Obstet. Gynecol. 113 (1972) 927).

There are also known vaginal rings, which like those for the treatment of prolapse, are provided with a metal spring. These vaginal rings are relatively stiff and their use may lead to erosions of the mucous membrane in the region of the posterolateral vault of the vagina (Amer.

Med.Ass. 208 (1969) 949). British Patent Specification No. ¢,264,731-. describes devices which consist of a medicament-containing capsule on a ring of silicone rubber. However, owing to their construction such devices are ill suited for mass production and they also lack practicability in use.

As in the case of Patent Specification No, 42345, the problem with which the present invention is concerned is to provide a vaginal ring which contains a pharmacologically active substance, wherein the active - 4 substance or substances is/are released over a period of at least three weeks, preferably a longer period, in a regular and constant quantity necessary for producing the biological action desired, and which avoid or minimise the above-mentioned disadvantages of the hitherto known vaginal rings. ! The present invention provides a vaginal ring device which comprises a support-ring and at least one ring-section which has an exposed surface, extends circumferentially round a part or the whole of the support-ring and incorporates a pharmacologically active substance, the cross-section of the support-ring being crescent-shaped or elliptical, or the supportring being formed as a hollow ring which may have a circular or elliptical or crescent-shaped cross-section and which hollow ring may also have one or more internal walls or partitions, or the support ring being formed as a jacketed core combination.

Throughout the Specification, including the claims, references to the cross-section of a ring are to be understood as references to the cross-section, taken in a plane containing the axis of the ring, of that part of the ring that lies on one side of the said axis.

As the support-ring in a general sense determines the shape of the vaginal ring, the external features apply also to the vaginal ring device of the invention.

A preferred construction of vaginal ring device of the invention is one in which the support ring has one or more grooves (generally in the form of pocket-shaped recesses) extending round a part or the whole of its circumference and a ring-section incorporating a pharmacologically active substance is seated in a groove or two or more ring-sections each - 5 4473Θ incorporating a pharmacologically active substance are seated in a groove or grooves.

The support-ring may have two grooves each extending in succession round a part of the outer circumference of the support-ring and each seating a ring-section incorporating a pharmacologically active substance, the two ring-sections incorporating different active substances. Alternatively, the two grooves may extend side by side round a part or the whole of the outer circumference of the support-ring.

In a further construction of vaginal ring device in accordance with the invention, the support-ring has a single groove extending round a part or the whole of the outer circumference of the support-ring, and two ring-sections each incorporating a different pharmacologically active substance are seated in different parts of the single groove. Corresponding to the dimensions of the active-substance-containing ring-sections, the grooves or recesses optionally also have different depths or widths.

In another form of vaginal ring device according to the invention, one ring-section extends round a part or the whole of the outer circumference of the support-ring and a second ring-section extends round the inner circumference of the support-ring, the two ring-sections not making con20 tact with each other.

The medicament-containing ring-sections advantageously have a circular cross-section, but the cross-section may also have the shape of a segment of a circle. The d.imensions of the support-ring and of the active-substance-containing ring-sections are advantageously so chosen that the lines of contact of the outer or inner edges of the support-ring with the medicament-containing ring-section lie, in a radially outward direction - 6 3 with respect to the cross-section of the ring, beyond the centre line of the medicament-containing ring-section in the case of a circular cross-section or beyond, in a radially outward direction with respect to the said cross-section, the curve on which lie the centres of the circles of which the cross-sections each form a part, in the case of a cross-section having the shape of a segment of a circle. In this way the medicament-containing ring-sections are positively located in the grooves or pocket-shaped recesses of the support-ring. In general, the ring-section(s) will not completely enclose the support ring. By a pharmacologically active substance there is to be understood herein a substance capable of having an effect on a living organism. The pharmacologically active substance (also referred to herein simply as the active substance) is preferably a medicament, the term medicament being understood herein to include not only substances capable of curing or preventing disease, but also other substances capable of having beneficial effects in animal (including human) organisms.

Several forms of vaginal ring devices constructed in accordance with the invention will now be described, by way of example, with reference to the accompanying drawings, in which: Figure 1 shows a section through a support-ring having a crescentshaped cross-sectioh having a height a and a maximum wall thickness Jj, the wall thickness being taken in a radial direction with respect to the ring as a whole; Figure 2 shows a section through a support-ring having a hollow crescent shaped cross-section; Figure 3 shows a section taken through a hollow ring of circular - 7 cross-section, having an inner tubular member and intermediate walls; Figure 4 shows a section taken through a hollow ring which has a generally crescent-shaped cross-section and internal walls or partitions; Figure 5 shows a section taken through a support-ring, in the form of a jacketted-core combination made by the sandwich mode of construction; Figure 6 shows a section taken through a hollow support-ring having a circular cross-section; Figure 7 shows Ss^ection taken through a support-ring, which consists of a combination of a core of a synthetic plastics material with another synthetic plastics material in the form of a jacet; ' Figure 7a shows a section taken through a modified form of the ring shown in Figure 7; Figure 8 shows a section taken through a support-ring having a generally crescent-shaped cross-section; Figure 9 shows a section taken through a support-ring of ellipsoidal cross-section; and Figure 10 shows a section taken through a hollow support-ring of ellipsoidal cross-section.

Referring to the accompanying drawings, the form of ring shown in Figure 1 comprises a support-ring 1 of crescent-shaped cross-section, an oestrogen-containing ring section 2 and a gestagen-containing ring-section 3. . The two ring-sections 2 and 3 each extend a part of the way round the outer circumference of the support-ring 1.

The second form of ring, which is shown in Figure 2, differs from the ring shown in Figure 1 in that the support-ring 4 is of hollow {instead of solid) crescent-shaped cross-section and in that the two ring-sections - 8 4 and 3 are replaced by a single gestagen-containing ring-section 5.

The third form of ring, which is shown in Figure 3, comprises a support-ring, which is indicated generally by the reference numeral 6, and which has a main, outer tubular member 7 of hollow circular crosssection connected to an inner tubular member 8 by walls 9 which, seen in cross-section, extend radially. Extending side-by-side around the outer circumference of the outer tubular member 7 are an oestrogencontaining ring-section 10 and a gestagen-containing ring-section 11.

The fourth form of ring, which is shown in Figure 4, comprises a hollow support-ring, which is indicated generally by the reference numeral 12, and which is of generally crescent shaped (or C-shaped) Cross-section. The support-ring 12 is also provided with internal walls or partitions 14 which, seen in cross-section, extend radially. A gestagen-containing ring section 15 extends round the outer circumference of the support-ring 12.

The fifth form of ring, which is shown in Figure 5, comprises a support-ring, which is indicated generally by the reference numeral 16, and which is of circular cross-section. The support-ring 16 is made up of a core portion 17 surrounded by a tubular jacket portion 18. A gestagen-containing ring-section 19 is located in a recess which extends round the outer circumference of the tubular jacket portion 18.

The sixth form of ring, which is shown in Figure 6, comprises a support-ring 20, which is of hollow circular cross-section and which is formed with two grooves which extend side-by-side round the outer circumference of the support-ring. The smaller of the two grooves contains an oestrogen-containing ring-section 21 and the larger of them contains a - 9 gestagen-containing ring-section 22.

The seventh form of ring, which is shown in Figure 7, comprises a support-ring, which' is indicated generally by the reference numeral 23, and which is of circular cross-section. The support-ring 23 is made up of a core portion 24 surrounded by a tubular jacket portion 25. The portion 25 is formed with too grooves which extend round its outer circumference. The smaller of the too grooves contains an oestrogen-containing ring-section 26 and the larger of them contains a gestagen-containing ring-section 27.

The eighth form of ring, which is shown in Figure 7a, comprises a support-ring, which is indicated generally hy the reference numeral 23, and which is of circular cross-section. The support-ring 28 is made up of a core portion 29 surrounded by a tuhular jacket portion 30. The portion 30 is formed with a groove which extends round its outer circum15 ference. The groove contains a gestagen-containing ring-section 31 around which there extends an oestrogen-containing ring-section 32.

The ninth form of ring, which is shown in Figure 8, comprises a support-ring 33, which is of generally crescent-shaped (or C-shaped) cross-section. A groove extending round the outer circumference of the support-ring 33 houses a gestagen-containing ring-section 34.

The tenth form of ring, which is shown in Figure 9, comprises a support-ring 35, which is of elliptical cross-section. Two grooves extend side-by-side round the outer circumference of the support-ring 35, the larger groove housing a gestagen-containing ring-section 36 and the smaller groove housing an oestrogen-containing ring-section 37.

The eleventh form of ring, which is shown in Figure 10, comprises a support-ring 38, which is of hollow elliptical cross-section. Extending - 10 round the outer circumference of the support-ring 38 is a groove which houses a gestagen-containing ring-section 39.

The support-ring may consist of any physiologically tolerable synthetic plastics material or natural rubber, provided that it has sufficient strength and elasticity. Suitable synthetic plastics are, for example, organo-polysiloxane elastomers such, for example as LTVdimethyl-polysiloxane elastomer, heat vulcanized dimethyl-polysiloxane elastomers, polyamides, synthetic rubber, polyesters, polytetrafluorethylene and polyethylenes, which may be worked up in known manner into moulded bodies, for example, by injection-moulding or casting.

Another preferred construction of the invention is one in which there are vulcanised on to a support-ring of LTV-silicone elastomer ringsections based on LTV-silicone elastomer which incorporates a pharmacologically active substance.

This construction is composed of the following parts: A support-ring proper having one or two ring-sections incorporating a pharmacologically active substance and which are vulcanized on to the inner and/or the outer edge of the support-ring.

The active-substance-containing ring-sections have a cross-section of a part of an annulus. The dimensions of the support-ring and of the vulcanized-on outer and inner active-substance-containing ring-sections are so chosen that the outer and inner vulcanized-on active-substancecontaining ring-sections, respectively, of the support-ring do not make contact with each other. The ring-sections incorporating a pharmacologically active substance may extend round the whole of the circumference of the support-ring or be vulcanized-on in sections extending round a part - 11 44736 of the circumference of the support ring.

The vaginal rings of the invention have a size range (external diameter) of 0.5 to 20 cm, and the size depends on the purpose of use.

In the case of the smaller mammals, such as dogs, the size of the ring is smaller than in the case of larger mammals, such as horses and cows. In the case of vaginal rings for women, the external diameter may be from 5 to 10 cm and, for example, in the case of rhesus monkeys it may be from 2 to 3 cm. The diameter of the cross-section of the ring may be from 5 to 15 mm, and preferably 7 to TO mm.

The support-ring and the active-substance-cantaining ring-sections thereon may be made from known LTV-silicone elastomers. Silicone elastomers of the LTV-type and organo-polysiloxane two-component moulding compositions of the LTV-type (low temperature vulcanizing type) and the ingredients of these compositions are known, for example, from German Auslegeschriften 1,171,641 and 1,900,969, German Offenlegungsschrift 1,940,124, U.S.

Specifications Nos. 2,823,218, 3,159,601, 3,159,662 and 3,220,972.

There are suitable, for example, LTV-silicone elastomer two-component compositions which consist of 89-91% of linear dimethyl-polysiloxane containing a maximum of 0.5 mol-% of methyl-vinyl-siloxane units and 9-11% of dimethyl-polysiloxane containing SiH-bonds and having a molecular weight of 500 to 1000, which contain up to 3 SiH-bonds, and are vulcanized in the presence of platinum or a platinum compound as catalyst such, for example, as hexachloroplatinic acid, (LTV-silicone elastomer A); LTV-silicone elastomer two-component compositions which contain 85 to 89% of dimethyl25 polysiloxahe having a maximum of 0.5 mol-% of methyl-vinyl-siloxane units, -6% of dimethyl-polysiloxane contaiing Si-H-bonds, 5-10% of a dimethyl- 12 **736 polysiloxane resin having a cross-linking and reinforcing action and containing a maximum of 1.2 mol-% of methyl-vinyl-siloxane units, and are vulcanized, for example, with a platinum compound as catalyst (LTVsilicone elastomer B); and LTV-silicone elastomer two-component moulding compositions containing dimethyl-polysiloxane copolymer (LTV-silicone elastomer C).

The LTV-silicone elastomer C is preferably used in the case of pharmacologically active substances having one or more unsaturated groups in the molecule and comprises:10 I. 20 - 100 Parts by weight of an organo-polysiloxane having a viscosity of 500 - 200,000 cSt (at 25°C) and the general formula: R CH,= CHSiO I R SiO I R R I - Si — CH = CH, I n R in which R represents an alkyl (preferably methyl) and/or aryl radical, and n represents a whole number from 200 to 1600.

II. 1-50 Parts, preferably 10-35 parts, by weight of an organo-polysiloxane copolymer comprising: (a) (R')3SiOo.5-units, (b) (R')z-CH=CH2-SiOO-5-units, and (c) SiO2-units in which R' represents a monovalent organic radical containing no unsaturated groups and at least 50% of R' are methyl radicals, and the ratio a + b/c is 0.4 - 1.5 (preferably 0.6 - 1.0) and the ratio b/c is 0.02 - 0.5 (preferably 0.05 - 0.15). - 13 447 3 6 III. 5 - 15 Parts by weight of an organo-hydrogen-polysiloxane of the general formula -------- R a^b9i®*t-s-b -Τ~ίin which R represents a monovalent radical containing no unsaturated 5 groups and the ratio a:b has a value of 0.5 - 10 (preferably 1.0 - 5) and the sum a + b is equal to 1 to 2.5, and at least three hydrogen atoms are present bound to different Si-atoms per molecule, which contains 50 - 500 mol-% of the unsaturated groups present in components I and II on Si-H-bonds, and a IV. catalytic quantity of platinum or a platinum compound.

The alkyl and/or aryl radicals R present in component I may contain Up to 10 carbon atoms. There may be mentioned, for example, methyl, ethyl, propyl, isopropyl, butyl, octyl, tdrtiary-amyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tolyl, xylyl, benzyl, chlorophenyl, cyano15 methyl and 3,3,3-trifluoropropyl radicals.

The residues R and R present in components I and II may be the same or different and represent alkyl radicals containing up to 8 carbon atoms, and preferably those containing up to 3 carbon atoms. There may be mentioned, for example, methyl, ethyl, and ri-propyl.

The constituents I, II and IV form one component of the LTV-organopolysiloxane two-component moulding composition and constituent III is the second component having a cross-linking action.

For the purpose of retarding hardening out at room temperature, component I or the mixture of components I, II and IV or I, II, III and IV, contain metal ions, for example, copper(II) ions, in a quantity of 2.00 to 75 parts by weight of metal ions for each part by weight of - 14 6 platinum.

Although the vulcanization of the organo-polysiloxane moulding compositions in the presence of noble metal catalysts can also be carried out at room temperature or body temperature, it is especially advantageous to carry out the vulcanization at a temperature within the range of from 40° to 120°C. The vulcanization time of the catalysed mixture is 1 to 6 hours at a temperature within the range of from 60 to 120°C. For pre-vulcanization the mixture may be heated at a higher temperature for a short time, for example, up to 150°C for 1-10 minutes, but a maximum of 15 minutes.

The platinum component IV of the moulding composition may be used in one of the forms that are described in the literature for catalysing the reaction between silicon-bound hydrogen residues and silicon-bound vinyl residues. There may be mentioned metallic platinum per se or platinum on carrier substances, such, for example, as silica gel or carbon powder, or hexachloroplatinic acid and platinum salts such, for example, as platinum carbonyl dichloride Pt CO Cl2 and platinum dicarbonyl dichloride Pt(CO)2Cl2. All these platinum compounds can be used as vulcanization catalysts. However, pure hexachloroplatinic acid has the disadvantage that it is relatively difficultly soluble in organo-silicon compounds that contain silane groupings. Platinum compounds that are used as catalysts in solid form cause the cross-linking reaction to take place very slowly and in a manner difficult to regulate, and also the reaction itself can be more easily interrupted than is to be expected when the comparable catalysts are used in solution. Hexachloroplatinic acid used as a catalyst is therefore dissolved preferably in isopropanoi, - 15 44736 and Pt CO Cl2 and Pt(CO)2Cl2 are dissolved in a vinyl group-containing diorgano-polysiloxane containing 10 to 15 mol-2 of vinyl groups. There must be used at least 0.1 part by weight of platinum per million parts by weight of components I and II. As impurities in the moulding com5 positions can poison such small amounts of catalyst, there are preferably used 10 to 40 parts per million of platinum. Larger quantities of platinum do not impair the reaction.

In a special construction of the vaginal ring device of the invention there is used the same LTV-silicone elastomer both for the support-ring and also the pharmacologically active-substance-containing ring-sections.

In a special construction of the support-ring used for the vaginal ring device of the invention, the support-ring comprises a foamed silicone rubber having c-losed pores. For this purpose there is added to the vulcanizing mixture in a finely divided form an agent that evaporates during the vulcanization such, for example, as a hydrocarbon such, for example, as pentane or heptane and a halogenated hydrocarbon such, for example, as methylene chloride, monofluoro-dichioromethane, dichlorofluoromethane or trichloro-trifluoromethane.

The vulcanizates obtained from these organo-polysiloxane two20 component moulding compositions are inactive towards non-ionic lipophilic medicaments, are physiologically tolerable to the living organism, and are not absorbed thereby.

The pharmacologically active substances present in the elastomer material, for example, elastomer rings, are preferably active substances having a hormonal activity such, for example, as oestrogens and gestagens. There may be mentioned, for example, 3-methoxy-17a-ethi nyl-1,3,5(10)- 16 “’3β oestratrien-17-ol (mestranol), 3-hydroxy-1,3,5(10)-oestratrien-17~one (oestrone), 17g-oestradio1, oestriol and ethinyl-oestradiol and also 4-pregnen-3,20-dione (progesterone), 4-13Lethyl-17a-ethinyl-17e-hydroxy4-gonen-3-one (d-norgestrel) and esters thereof, 17a-ethinyl-19-nortest5 osterone (norethisterone) and esters thereof, 6-chloro-17-hydroxy-la,2amethylene-pregna-4,6-dien-3,20-dione (cyproterone) and esters thereof, 19-nor-hydroxyprcgesterone and esters thereof, 6-chloro-17-acetoxy-pregna4,6-dien-3,20-dione (chloromadinone acetate), 15,16a-methy1ene- and 15, 16e-methylene-17g-hydroxy-l8-methyl-17a-ethi nyl-4-oestren-3-one, 17 a10 acetoxy-6a-methyl-progesterone (medroxy-progesterone acetate) and 9β,10αpregna-4,6-dien-3,20-dione (dydrogesterone).

As pharmacologically active substances there come into consideration all medicaments, especially those that are non-ionic and lipophilic.

Thus, there are also suitable neuroleptics such, for example, as butyro15 phenone derivatives, for example, haloperidol, or bacteriostatics and fungistatics such, for example, as nystatin or metronidazole, for incorporation in the silicone elastomer.

The quantity of pharmacologically active substance incorporated in the material of the or each ring-section (more especially the LTV-silicone elastomer) may be from 10 to 60% by weight and in each particular case depends on the specific active substance or combination of active substances. For example, there may be mentioned the following total dosages: - 17 44736 Cyproterone acetate: 200 to 1000 mg D-norgestrel: 100 to 500 mg Ethinyl-oestradiol: 20 to 100 mg Oestradiol: 20 to 90 mg Mestranol: 50 to 100 mg Ethinyl-nortestosterone acetate: 150 to 950 mg Oestrone: 10 to 80 mg Oestriol: 15 to 70 mg Progesterone: 250 to 900 mg Norethisterone: 100 to 600 mg Cyproterone: 100 to 900 mg Norhydroxyprogesterone: 250 to 950 mg Chioromadinone acetate: 170 to 850 mg 15,16a-methylene- and 15,16g-methylene-17|·- hydroxy-18-methyl-l7a-ethi nyl-4-oestren-3-oqe: 50 to 750 mg Dydrogesterone: 100 to 550 mg Metronidazole: 300 to 950 mg It is possible, for example, for an outer ring-section to contain only a gestagen and-an inner ring-section an oestrogen, or vice versa. Gestagens or oestrogens may be used, for example, in combination with bactericides.

The total quantity of active substance in the material of the or each ring-section (more especially LTV-silicone elastomer) is so chosen that during the desired period a predetermined constant quantity is released per day. Examples are as follows: - 18 Cyproterone acetate; D-norgestrel: Ethinyl-oestradiol: Oestradiol: Hestranol: Ethinyl-nortestosterone acetate: 300 to 1000 ugm/d 30 to 250 ugm/d 30 to 60 pgm/d 20 to 150 ugm/d 20 to 100 ugm/d 300 to 1000 ugm/d.

One construction of the vaginal ring of the invention is for use in preventing conception. A contraceptive effect based on inhibiting ovulation may be achieved within the period of use of the vaginal ring of the invention when it releases, for example, daily between 130 and 250 ugm of d-norgestrel and 30 to 50 ugm of ethinyl-oestradiol or between 800 and 1000 ugm of cyproterone acetate and 30 to 50 ugm of ethinyloestradiol. Vaginal rings that contain in the active-substance-containing ring-sections agents that are active against protozoa such, for example, as metronidazole and optionally oestrogens, are especially suitable for the treatment of trichomoniasis. The active substance is incorporated in the material (more especially an LTV-silicone rubber base) used for making the ring-section containing the active substance. For this purpose the active substance is disintegrated or finely ground, optionally micronised, mixed with, for example, an LTV-silicone rubber two-component composition to form a suspension free from air bubbles, moulded into rings, and vulcanized by heating, preferably at 40 - 120°C.

The active-substance-containing ring-sections may have, in the case of an outer ring-section a diameter of 0.5 to 8.0 mm, preferably 1.5 to 5.0 mm and, in the case of an inner ring-section, a diameter of 0.3 to 2.0 mm, preferably 0.4 to 1.6 mm. - 19 44736 The active-substance-containing ring-sections may be built up wholly or partially on the matrix principle. However, the ring-sections may instead consist of a core containing an active substance and an outer sheath of silicone elastomer of any desired layer thickness which is free from active substance or lower in concentration of the active substance than in the core, or, conversely, they may consist of an enclosing layer of elastomer and a core-member low in active substance. Such a sheath which is lower in concentration of the active substance over a core higher in concentration of active substance in which the active substance is preponderantly in suspension is obtained, for example, by subjecting a preparation built up on the matrix principle to an extraction for a short time with a suitable solvent such, for example, as ethanol/water 1/1 (vol./vol.).

The ring-sections containing the active substance may be inserted into grooves (generally formed as pocket-shaped recesses) in the supportring, and if desired adhesively secured in such recesses by the use of a catalysed LTV-silicone elastomer two-component component composition and subsequent vulcanization, or moulded on the pre-vulcanized supportring and vulcanized together with the support-ring.

The support-ring and the active-substance-containing outer and/or inner ring-section, joined or adhesively secured together, form the vaginal ring device proper.

For producing a ring-section in the 1orm of a coating or layer on the support-ring the active substance may likewise be incorporated in an LTV-silicone elastomer base. For this purpose the active substance is finely ground, if desired micronised, mixed with an LTV-silicone - 20 -/ *73β elastomer two-component composition to form a suspension, applied as a layer by means of the multi-colour injection moulding technique to the pre-vulearn'zed support-ring, and vulcanized by heating, preferably at 40 - 120°C.

It may also be of advantage to add to the suspension containing the active substance and silicone elastomer an auxiliary substance such, for example, as a tenside, an anti-foaming agent, a solubiliser or absorption-retarder, or a mixture of any two or more such substances, in order to impart the desired physical properties to the moulded body.

Furthermore, there also come into consideration inert auxiliary substances such, for example, as highly dispersed silicon dioxide, which give the ring the desired mechanical properties.

Advantageously, the active-substance-containing coatings, when vulcanized on to the outer surface of the support-ring, have a thickness of 0.1 to 5.0 mm, and preferably 0.5 to 3.0 mm, and, when vulcanized on to the inner surface of the support-ring, a thickness of 0.1 to 3.0 mm, and preferably 0.5 to 2.0 mm.

The active-substance-containing coatings are preferably built up wholly or partially on the matrix principle.

As no by-products are formed during the vulcanization of an LTVsilicone elastomer two-component composition, subsequent heat treatment of such hardened products is unnecessary.

The vaginal ring devices of the invention have the advantage that the pharmacologically active substance or substances are released therefrom relatively regularly and in constant amounts over a long period within the limits of the dosage necessary for the desired biological action, - 21 4473° for example, for inhibiting ovulation, They have the further advantage that the quantity of the active substance that has to be incorporated in a single such contraceptive can be much smaller than in the case of the known vaginal rings.

Vaginal ring devices of the invention based on LTV-silicone elastomer have a materially reduced tendency to crumble under mechanical stress.

When introduced into the body such ring devices are not so easily damaged as are vaginal rings based on RTV-elastomers, which contain for improving the mechanical properties more or less defined mixtures of active fillers having known disadvantageous properties towards the pharmacologically active substance.

With the vaginal ring device of the invention there can be successfully used many active substances that could not be successfully used with the hitherto known and usual carrier materials in the known vaginal rings.

Vaginal rings made in accordance with the invention can be sterilised on saturated steam under pressure at 120°C, without undergoing undesired changes.

The following Examples illustrate the invention: Example 1 A support-ring intended to receive two medicament-containing rings is produced by the hollow body blast method in the form of a tubular ring (see Figure 6) of polyethylene/vinyl acetate copolymerisate (LUPOLEN V 3520 K/BASF) having the following dimensions (LUPOLEN is a Trade Mark): External diameter 60 mm, internal diameter 44 mm and diameter of the hollow space in the circular cross-section of the ring 3 mm. - 22 The support-ring is provided with two pocket-shaped recesses extending around it, which are intended to receive medicament-containing ringsections 21 and 22 as shown in Figure 6. One medicament-containing outer ring-section has a diameter of 2.0 mm, and the other medicamentcontaining ring-section has a diameter of 1.0 mm. The vaginal ring, after insertion of the medicament-containing rings, has in the place of insertion of those rings a diameter of the ring cross-section of 8.5 mm.

The medicament-containing ring-section having a diameter of 2 urn is formed from a suspension of 5 parts by weight of D-norgestrel, 15 parts by weight of highly dispersed silicon dioxide rendered waterrepellent (AEROSIL R972/DEGUSSA) and 8 parts by weight of very finely pulverised magnesium oxide, in 72 parts by weight of LTV-organo-polysiloxane two-component moulding composition A, is pre-vulcanized by heating for 1| minutes at 120°C., and is vulcanized by heating for 3 hours at 80°C. The LTV-organo-polysiloxane two-component moulding composition A consists of 75 parts by weight of a polydimethylsiloxane vinyl-terminally blocked at both ends having a viscosity of 50,000 cST at 25°C., 25 parts by weight of a copolymer having the composition: 40 mol-% of Si02-units, mol-% of (CH3)-SiOo.5-units, 15 mol-% of Vi(CH3)2SiQ0.5-units, 8 parts by weight of an SiH-component consisting of: 16.6 mol-% of (CH3)3SiOo.5~ units, 33.4 mol-% of (CH3)2SiO-units, 50 mol-% of CH3HSiO-units and 52 ppm of platinum in the form of a solution of 1% strength of Pt(C0)2Cl2 calculated on the quantity of dimethyl-polysiloxane vinyl-terminally blocked at both ends.

The other medicament-containing ring-section is produced from a homogeneous suspension of 3 parts by weight of ethinyl-oestradiol and - 23 44736 parts by weight of highly dispersed silicon dioxide rendered waterrepellent (AEROSIL R972/DEGUSSA) in 71 parts by weight of LTV-organopolysiloxane two-component moulding composition B by moulding, prevulcanizing at about 120°C for 1J minutes and vulcanizing for two hours at 105°C. The LTV-organo-polysiloxane two-component moulding composition B consists of 82.5 parts by weight of a polydimethylsiloxane vinylterminally blocked at both ends having a viscosity of 1000 cST at 25°C., parts by weight of a copolymer of the composition: 40 mol-5! of Si02Units, 45 mol-% of (CH3)3SiOo<5-units, 15 mol-% of Vi(CH3)2SiOo,5-units, 7.0 parts by weight of an SiH-component consisting of: 38 mol-% of Si02units, 29 mol-% of (CH3)3Si0o.5-units, 33 mol-% of (CH3)2HSiOo.5-units and 40 ppm of platinum in the form of a solution of 2% strength of i H2PtCl6 in isopropanol (calculated on the quantity of polydimethylsiloxane vinyl-terminally blocked at both ends).

The medicament-containing ring-sections are inserted in the supportring and form, together with that ring, the vaginal ring device itself.

AEROSIL is a Trade Mark.

Example 2 From dimethyl-polysiloxane moulding composition (SILASTIC 4600/D0W CORNING) is formed by moulding, prevulcanizing at 150°C for 5 minutes and vulcanizing for one hour at 120°C., a tubular material having a crescent-shaped cross-section and a diameter of 9 mm and an internal diameter of 5 mm, which has a pocket-shaped recess of 1.5 mm on its outer surface. Sections of this tubular material are moulded with the use of catalysed SILASTIC 4600 to form hollow rubber rings (see Figure 2) as support-rings, and vulcanized for 30 minutes while heating at 130°C. - 24 The support-rings have an external diameter of 60 mm and and internal diameter of 42 mm and the pocket-shaped recess extends along its outer surface to receive a medicament-containing ring-section having a diameter of 2 mm. This outer ring-section contains D-norgestrel and is prepared fron the moulding composition mentioned in Example 1 in the manner given therein, and is inserted in the support-ring.

SILASTIC is a Trade Mark.

Example 3 A vaginal ring containing D-norgestrel is produced in a three-stage process in the form of a combination vulcanizate of a support-ring with ring-sections containing D-norgestrel (see Figure 5). The support-ring of this vaginal ring is moulded by the sandwich-injection moulding process with a groove (not shown) extending round it from polyisobutylene having an average molecular weight of about 2,700,000 (OPPANOL B 150/BASF) as the core and LTV-silicone rubber two-component composition B (as described in Example 1) in admixture with 20 parts by weight of highly dispersed silicon dioxide rendered water-repellent (AEROSIL R972/DEGUSSA) as the outer jacket portion. The dimensions of the support-ring are: External diameter 62 mm, internal diameter 44 mm, the groove extending round it to receive the D-norgestrel-containing outer ring: 1 mm deep, mm wide.

The D-norgestrel-containing ring-section is formed from the moulding composition described in Example 1 by injection into the recess extending round the support-ring and connected to the outer layer of the supportring by subsequent pre-vulcanization for 1.2 minutes at 115°C followed by vulcanization for two hours at 110°C. The ring-section has a cross- 25 4473S section the shape of a segment of a circle and at its outer edge a radius of curvature of 120 mm.

OPPANOL and AERPSIL are Trade Harks.

Example 4 A vaginal ring containing D-norgestrel and ethinyl-oestradiol is made in the form of a compound vulcanizate having a crescent shaped cross-section (see Figure 1) by the multi-colour injection-moulding technique. The ring has an external diameter of 60 mm. The distances jt and A are 7.6 mm and 2.8 mm, respectively. There are injected on to the support-ring in succession at the outer edge the D-norgestrel-containing and ethinyl-oestradiol-containing ring-sections, pre-vulcanized by heating for 2 minutes at 115°C., removed from the mould and vulcanized outside the mould by heating for 2 hours at 80°C. The support-ring is produced from a mixture of 23 parts by weight of highly dispersed silicon dioxide (AEROSIL R972/DEGUSSA) and 77 parts by weight of the LTV-silicone rubber two-component composition A described in Example 1.

The D-norgestrel-containing ring-section 2 mm in diameter projects 0.6 mm, shaped as the segment of a circle, from the outer edge of the support-ring. It consists of a mixture of 24 parts by weight of highly dispersed silicon dioxide, 8 parts by weight of micronised D-norgestrel and 68 parts by weight of catalysed LTV-silicone rubber base (SILOPREN 3008/BAYER).

The ethinyl-oestradiol-containing ring-section having a diameter of 1 mm projects 0.4 mm, shaped as the segment of a circle, from the outer edge of the support-ring. It contains per 100 parts by weight 10 parts by weight of micronised ethinyl-oestradiol and 21 parts by weight of - 26 highly dispersed silicon dioxide in addition to 69 parts by weight of LTV-organo-polysiloxane moulding composition consisting of 75 parts by weight of a polydimethyl-siloxane vinyl-terminally blocked at both ends having a viscosity of 1000 cSt at 25°C., 25 parts by weight of a co5 polymer of the composition: 40 mol-2 of SiO2-units, 45 mol-2 of (CH3)2Si00-5-units, 15 mol-2 of Vi(CH3)2SiOo-units, 8 parts by weight of an Si-H-component consisting of 16.6 mol-2 of (CH3)3Si00-5-units, 33.4 mol-2 of (CH3)2Si0-units, 50.0 mol-2 of CH3HSi0runits and 10 ppm of platinum (calculated on the total mixture, in the form of a solution of 22 strength of H2PtCl6 in isopropanol).

AEROSIL and SILOPREN are Trade Marks.

Example 5 A vaginal ring containing ethinyl-oestradiol as well as ethinylnortestosterone acetate is made in the form of a mechanical combination of an ethylene-vinyl acetate copolymerisate (ALATHON 3180/DU PONT) as a hollow support ring having two medicament-containing ring-sections of LTV-silicone elastomer base fitting into grooves extending round it (see Figure 3).

The support-ring is formed from hollow sections by welding their ends and has an external diameter of 64 mm and an internal diameter of mm, partition and wall thicknesses of 1.5 mm, and has grooves extending round its outer edge that are 1 mm deep and 3 mm wide, and 1 mm deep and 1 mm wide, respectively. The ethinyl-nortestosterone acetate-containing ring-section, 1 mm thick and 3 mm wide and having an internal diameter of 62 mm, is formed from a mixture of 10 parts by weight of micronised ethinyl-nortestosterone acetate and 22 parts by weight of highly dispersed - 27 silicon dioxide in 68 parts by weight of an LTV-organo-polysiloxane twocomponent moulding composition consisting of 75 parts by weight of a polydimethylsiloxane vinyl-terminally blocked at both ends and having a viscosity of 1000 cSt at 25°C., 25 parts by weight of a copolymer having the composition: 40 mol-% of SiO2-units, 45 mol-% of (CH3)2SiOo.5-units, mol-% of Vi(CH3)2SiOo.5-units, 8 parts by weight of an Si-H-component consisting of 16,6 mol-% of (CH3)3SiOo,5-units, 33.4 mol-% of (CH3)2SiOunits, 50.0 mol-% of CH3HSiO-units and 30 ppm of platinum (calculated on the total mixture, in the form of a solution of 1% strength of Pt(C0)2Cl2 dissolved in an open-chained vinyl group-containing dimethylpolysiloxane containing 12 mol-% of vinyl groups) and 5 parts by weight, calculated on the parts by weight of platinum, of Cu-(II)-ions, and is then vulcanized at 105°C.

The ethinyl-oestradiol-containing ring-section is 1 mm thick and 1 mm wide and has an internal diameter of 58 mm, and is moulded from the composition described in Example 4 and vulcanized by being heated at 80°C.

“ALATHON is a Trade Mark.

Example 6 A vaginal ring .containing 15,16a-methylene-17β-hydroxy-l8-methyl20 17a-ethinyl-4-oestren-3-one as well as oestriol has! the following structure: A solid soft rubber ring based on natural rubber having an external diameter of 36 mm and a diameter of the ring cross-section of 6.6 mm is used as the core member and is jacketed by injection-moulding with a 1.2 mm thick layer of LTV-silicone rubber (see Figure 7). The silicone rubber jacket has on the outer edge of the ring two 0.5 mm deep grooves having widths of 1.6 and 3.0 mm respectively. This ring is the support- 28 4473δ ring for two medicament-containing ring-sections of which the crosssection is the shape of a segment of a circle, which are mechanically connected to the support-ring. The jacketing of the soft rubber ring is carried out with the LTV-organo-polysiloxane two-component moulding composition A described in Example 1 and vulcanized at 13O°C.

The ring-section containing 10 parts by weight of micronised 15.16amethylene-17 p-hydroxy-l8-methyl-17a-ethi nyl-4-oestren-3-one, havi ng a chord length of 3.0 mm, is made on the basis of a mixture consisting of 20 parts by weight of highly dispersed silicon dioxide (AEROSIL 200) and 70 parts by weight of the LTV-silicone rubber two-component composition B described in Example 1.

The ring-section containing oestriol, having in cross-section the shape of a segment of a circle, and a chord length of 1.6 mm, is produced from a mixture of 12 parts by weight of micronised oestriol. 19 parts by weight of highly dispersed silicon dioxide and 69 parts by weight of the above described LTV-silicone rubber two-component composition B by moulding and vulcanizing for three hours at 90°C.

AEROSIL is a Trade Mark.

Example 7 A vaginal ring containing D-norgestrel and ethinyl oestradiol takes the form of a support-ring comprising a jacketted-core combination and two ring-sections partially surrounding the support-ring and separately containing the medicaments and which are chemically connected with the ring (see Figure 7a). The core of the support-ring is made of rubberlike polyurethane in the form of a solid ring having an outer diameter of 60 nm and a diameter of the ring cross-section of 8 mm. This support- 29 «4736 ring core is provided with a coating 1.5 mm thick by repeated immersion in a solution of 20% strength of the catalysed LTV-silicone rubber twocomponent composition B (see Example 1) in methylene chloride and the coating is prevulcanized for two minutes at 125°C and vulcanized at 130°C for one hour.

The groove in this support-ring, which is 1.5 mu deep and 3 mm wide and in injection-moulding functions as the insertion part, is filled by the.process of two-colour injection moulding with the composition containing D-norgestrel described in Example 4, and prevulcanized for 1| minutes at 110°C. On the resulting band-like ring-section containing D-norgestrel extending round the outer edge of the vaginal ring is centrally injection moulded with the moulding composition containing ethinyl-oestradiol of Example 1 a round chord-like ring-section having a diameter of 1 mm, and pre-vulcanized for two minutes at 110°C. The vaginal ring so prepared is vulcanized by being heated for one hour at 110°C.

Example 8 Vaginal rings containing D-norgestrel are made with the use of the support-ring described in Example 7 by vulcanizing-on the moulding composition containing D-norgestrel described in Example 1 in the groove of the support-ring (see Figure 7a).

Example 9 A vaginal ring containing D-norgestrel and ethinyl-oestradiol is made in the form of a mechanical combination of a support-ring having an ellipsoidal cross-section (see Figure 9; a = 2 mm, j) = 3.5 mm) and two recesses of 0.8 and 1.4 mm, respectively, extending round the outer edge - 30 at a distance apart of 1.5 mm, and a width of groove of 1.0 and 2.0 mm, respectively, with a medicament-containing ring-section having in crosssection the shape of a segment of a circle fitting into each of these grooves. The support-ring is injection moulded with ethylene-vinyl acetate copolymerisate (ALATHON 3185/DU PONT). The ring-section containing D-norgestrel is moulded from the composition given in Example 1 and vulcanized for 90 minutes at 110°C.

The ring-section containing ethinyl-oestradiol is moulded from the composition given in Example 1 and vulcanized by heating at 105°C.

ALATHON is a Trade Mark.

Example JO A vaginal ring containing 4-pregnen-3,20-dione (progesterone) is made in the form of a combination vulcanizate consisting of a supportring having a groove extending along its outer edge in which the ring component containing progesterone is vulcanized. The support-ring is a solid ring of generally C-shaped crescent cross-section having an opening 2 mm wide at its inner edge (see Figure 8). The ring has an external diameter of 60 mm, an internal diameter of 42 mm and in crosssection an internal diameter of 5 nm. The groove extending round the outer edge of the ring is 1.5 mm deep and 3 mm wide.

The support-ring is formed from a mixture of 20 parts by weight of highly dispersed silicon dioxide and 80 parts by weight of LTVsilicone rubber two-component composition B, of which the composition is given in Example 1, and prevulcanized at 120°C. This support-ring is used in a second stage of the process like an insert part, in the groove of which, extending round it, is injection moulded the moulding - 31 O'?3® composition containing progesterone. This moulding composition consists of 15 parts by weight of micronised progesterone and 20 parts by weight of highly dispersed silicon dioxide in the LTV-silicone rubber twocomponent composition A (for composition see Example 1). After the injection moulding, it is prevulcanized in the groove of the hollow ring by heating at 90°C. The medicament-containing ring-section is then vulcanized by being heated for two hours at 80°C.

The progesterone-containing ring-section of the vaginal ring present as a combination vulcanizate is converted by a four-stage immersion process into a medicament-carrier having a sheath poor in active substance upon a core rich in active substance. In addition the vaginal ring is kept in succession in ethanol of 90% strength for 10 minutes and 5 minutes, of 70% strength for 5 minutes and of 50% strength for 5 minutes Example 11 A vaginal ring containing 17a-acetoxy-6a-methyl-progesterone (medroxyprogesterone acetate) is made in the form of a mechanical combination of a support-ring having a groove extending round its outer edge to receive a ring-section containing medroxyprogesterone acetate (see Figure 10). The support-ring is a hollow ring having an ellipsoidal cross-section, it has an external diameter of 60 mm, an internal diameter of 42 mm, a wall thickness of 3 mm and is formed from ethylene/vinyl acetate copolymer (ALATHON 3185/DU PONT) by the hollow body blast process, and has a groove of 1.5 mm depth and 2.5 mm width extending round its outer edge.

ALATHON is a Trade Mark.

The medroxyprogesterone acetate-containing ring-section is separately - 32 4473β injection moulded from a mixture of 20 parts by weight of micronised medroxyprogesterone acetate, 11 parts by weight of highly dispersed silicon dioxide and 69 parts by weight of LTV-silicone rubber two-component composition B (for composition see Example 1) and vulcanized at 100°C.

Example 12 A vaginal ring containing 15,16g-methylene-17g-hydroxy-18-methyl17a-ethinyl-4-oestren-3-one is made in the form of a mechanical combination of a support-ring open at its inner edge, which is moulded in the form of a hollow ring of C-shaped crescent cross-section with internal partition walls (see Figure 4) from polyethylene/vi nyl acetate copolymerisate (LUPOLEN V 3520 K /BASF) having a groove 2 mm wide and 1 mm deep extending round its outer edge to receive the medicament-containing band-ring.

The support-ring is formed from hollow sections by welding the ends and has an external diameter of 62 mm, an internal diameter of 40 mm, and an internal partition and wall thickness of 1.5 mm.

The medicament-containing ring-section is made from a mixture of parts by weight of 15,166-methylene-17B-hydroxy-18-methyl-17

Claims (20)

1. WHAT WE CLAIM IS:1. A vaginal ring device, which comprises a support-ring and at least one ring-section which has an exposed surface, extends circumferentially round a part or the whole of the support-ring and incorporates a pharmacologically active substance, the cross-section of the supportring being crescent-shaped or elliptical, or the support-ring being formed as a hollow ring which may have a circular or elliptical or crescent-shaped cross-section and which hollow ring may also have one or more internal walls or partitions, or the support-ring being formed as a jacketed core combination.

2. A vaginal ring device as claimed in claim 1, wherein the support-ring has one or more grooves extending round a part or the whole of its circumference and a ring-section incorporating a pharmacologically active substance is seated in a groove or two or more ring sections each incorporating a pharmacologically active substance are seated in a groove or grooves.

3. A vaginal ring device as claimed in claim 2, wherein the supportring has two grooves each extending in succession round a part of the outer circumference of the support-ring and each seating a ring-section incorporating a pharmacologically active substance, the too ring-sections Incorporating different pharmacologically active substances.

4. A vaginal ring device as claimed in claim 2, wherein the supportring has too grooves extending side by side round a part or the whole of the outer circumference of the support-ring, each groove seating a ringsection incorporating a pharmacologically active substance, the too ringsections incorporating different pharmacologically active substances. - 34 3 4736 5. Wherein the ring-section or sections have a circular cross-section. 24. A vaginal ring device as claimed in any one of claims 1 to 22, wherein the ring-section or sections have a cross-section having the shape of a segment of a circle. 25. A vaginal ring device as claimed in any one of claims 1 to 24, 10 which has been made by vulcanizing the ring-section or sections incorporating a pharmacologically active substance(s) to the support-ring. 26. A vaginal ring device as claimed in claim 1, constructed substantially as described herein with reference to and as shown in any one of Figures 1 to 10 of the accompanying drawings. 15 27.A vaginal ring device as claimed in claim 1, substantially as described in any one of Examples 1 to 12 herein. 28. A method of contraception wherein a vaginal ring as claimed in claim 18 or in any one of claims 19 to 27 as appended thereto is applied to a female mammal. 5 different parts of the single groove.

5. A vaginal ring device as claimed in claim 2, wherein the supportring has a single groove extending round a part or the whole of the outer circumference of the support-ring and two ring-sections each incorporating a different pharmacologically active substance are seated in

6. A vaginal ring device as claimed in any one of claims 2 to 4, wherein there are two ring-sections of different cross-sectional dimensions which are seated in grooves of different cross-sectional dimensions.

7. A vaginal ring device as claimed in claim 1, wherein the 10 support-ring is not completely enclosed by the ring-section(s).

8. A vaginal ring device as claimed in any one of claims 1 to 7~, wherein the ring-section or sections protrude beyond the outer surface of the support-ring.

9. A vaginal ring device as claimed in any one of claims 1 to 8,

10. A vaginal ring device as claimed in claim 9, wherein the synthetic plastics material is a LTV-silicone elastomer.

11. A vaginal ring device as claimed in any one of claims 1 to 10, wherein the ring-section or sections are made from a LTV-silicone elastomer. 20

12. A vaginal ring device as claimed in claim 10 or claim 11, wherein the LTV-silicone elastomer comprises:I. 20 - 100 Parts by weight of an organo-polysiloxane having a viscosity of 500 - 2OQ,0Q0cST (at 25°C) and the general formula: - 35 44736 CH 2 = CHSiO SiO Si-CH = CH 2 R R J n in which R represents an alkyl (preferably methyl) and/or aryl residue, and ji represents a whole number from 200 to 1,600. II. 1-50 Parts, preferably 10 - 35 parts, by weight of an organo5 polysiloxane copolymer comprising: (a) (R') 3 SiO o<5 -units, (b) (R') 2 -CH = CH 2 -SiO o .5-units, and (c) Si0 2 -units, in which R” represents a monovalent organic residue containing no un10 saturated groups and at least 50% or R' are methyl residues, and the ratio a + b/c is 0.4 - 1.5 (preferably 0.6 - 1.0) and the ratio b/c is 0.02 - 0.5 (preferably 0.05 - 0.15), III. 5-15 Parts by weight of an organo-hydrogen-polysiloxane of the general formula

13. A vaginal ring device as claimed in any one of claims 10 to 12, wherein the supportrring and the ring-section or sections are each made from the same LTV-silicone elastomer.

14. A vaginal ring device as claimed in any one of claims 1 to 13, wherein the pharmacologically active substance is a compound containing one or more unsaturated bonds in the molecule,

15. A vag'inal ring device as claimed in claim 14, wherein the pharmacologically active substance is a non-ionic lipoid soluble substance. 15 R aHbSiOfc^-h. in which R represents a monovalent residue containing no unsaturated groups and the ratio a:b has a value from 0.5 - 10 (preferably 1.0-5) and the sum a + b is equal to 1 to 2.5, and there being present, per molecule, at least three hydrogen atoms bound to different Si-atoms, 20 which contains. 50 - 500 mol-% of the unsaturated groups present in components (I) and (II) on Si-H-bonds, and IV. a catalytic quantity of platinum or a platinum compound. - 36 15 wherein the support-ring is formed from a synthetic plastics material.

16. A vaginal ring device as claimed in any one of claims 1 to 15, wherein the pharmacologically active substance is a steroid hormone.

17. A vaginal ring device as claimed in any one of claims 1 to 14, wherein the pharmacologically active substance is any one of the compounds specifically mentioned herein.

18. A vaginal ring device as claimed in any one of claims 1 to 17, wherein the pharmacologically active substance is a contraceptive.

19. A vaginal ring device as claimed in any one of claims 1 to 18, wherein the pharmacologically active substance is d-norgestrel. 20. A vaginal ring device as claimed in any one of claims 1 to 19, which comprises two ring-sections one of which incorporates a compound having gestagenic activity and the other incorporates a compound having oestrogenic activity. 21. A vaginal ring device as claimed in any one of claims 1 to 20, wherein the support-ring is formed from a foamed silicone rubber having closed pores. 22. A vaginal ring device as claimed in any one of claims 1 to 21, wherein one ring-section extends round a part or the whole of the outer ¢4736 circumference of the support-ring and a second ring-section extends round the inner circumference of the support-ring, the two ring-sections not making contact with each other. 23. A vaginal ring device as claimed in any one of claims 1 to 22,

20. 29. A method of contraception as claimed in claim 28, wherein the vaginal ring is applied to a human female.